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1.
CVIR Endovasc ; 7(1): 57, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39039376

RESUMO

PURPOSE: To evaluate outcomes and complications of prophylactic internal iliac balloon occlusion (PIIBO) in the management of patients with placenta accreta spectrum (PAS) at a large regional referral centre. MATERIALS AND METHODS: A retrospective review of all PIIBO for PAS performed over a 12-year period (2010-2022). Information for analysis was gathered from the local RIS/PACS and clinical documentation. Collected data included patient demographics, indication for procedure, sheath insertion and removal time, total duration of balloon inflation and complications that occurred. RESULTS: 106 patients underwent temporary internal iliac artery balloon occlusion within the 12-year period. All procedures utilised bilateral common femoral artery punctures, 6Fr sheath and 5Fr Le Maitre occlusion balloons. Catheters were successfully positioned and balloons inflated in obstetric theatre following caesarean delivery in 100% of the cases. The uterus was conserved in every case. There was no maternal mortality or foetal morbidity. Twenty patients (18.9%) had some form of complication that required further intervention. Of these, 7(6.6%) had post-operative PPH, which was treated with uterine artery embolisation; and 13 (12.3%) had arterial thrombus which required aspiration thrombectomy. All procedures were technically successful with no long-term sequelae. CONCLUSION: PIIBO plays an important part in reducing morbidity and mortality in patients with PAS. Clear pathways and multidisciplinary team working is critical in the management of these patients to ensure that any complications are dealt with promptly to avoid long-term sequelae.

2.
NAR Cancer ; 6(3): zcae030, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39015544

RESUMO

A subset of cancer cells are intrinsically sensitive to inhibitors targeting PARG, the poly(ADP-ribose) glycohydrolase that degrades PAR chains. Sensitivity is accompanied by persistent DNA replication stress, and can be induced by inhibition of TIMELESS, a replisome accelerator. However, the nature of the vulnerability responsible for intrinsic sensitivity remains undetermined. To understand PARG activity dependency, we analysed Timeless model systems and intrinsically sensitive ovarian cancer cells. We show that nucleoside supplementation rescues all phenotypes associated with PARG inhibitor sensitivity, including replisome speed and fork stalling, S-phase completion and mitotic entry, proliferation dynamics and clonogenic potential. Importantly nucleoside supplementation restores PARG inhibitor resistance despite the continued presence of PAR chains, indicating that sensitivity does not correlate with PAR levels. In addition, we show that inhibition of thymidylate synthase, an enzyme required for dNTP homeostasis, induces PARG-dependency. Together, these observations suggest that PARG inhibitor sensitivity reflects an inability to control replisome speed and/or maintain helicase-polymerase coupling in response to nucleotide imbalances.

4.
J Natl Compr Canc Netw ; 22(2D)2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38866043

RESUMO

BACKGROUND: Parallel panel germline and somatic genetic testing of all patients with ovarian cancer (OC) can identify more pathogenic variants (PVs) that would benefit from PARP inhibitor (PARPi) therapy, and allow for precision prevention in unaffected relatives with PVs. In this study, we estimate the cost-effectiveness and population impact of parallel panel germline and somatic BRCA testing of all patients with OC incorporating PARPi therapy in the United Kingdom and the United States compared with clinical criteria/family history (FH)-based germline BRCA testing. We also evaluate the cost-effectiveness of multigene panel germline testing alone. METHODS: Microsimulation cost-effectiveness modeling using data from 2,391 (UK: n=1,483; US: n=908) unselected, population-based patients with OC was used to compare lifetime costs and effects of panel germline and somatic BRCA testing of all OC cases (with PARPi therapy) (strategy A) versus clinical criteria/FH-based germline BRCA testing (strategy B). Unaffected relatives with germline BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 PVs identified through cascade testing underwent appropriate OC and breast cancer (BC) risk-reduction interventions. We also compared the cost-effectiveness of multigene panel germline testing alone (without PARPi therapy) versus strategy B. Unaffected relatives with PVs could undergo risk-reducing interventions. Lifetime horizon with payer/societal perspectives, along with probabilistic/one-way sensitivity analyses, are presented. Incremental cost-effectiveness ratio (ICER) and incremental cost per quality-adjusted life year (QALY) gained were compared with £30,000/QALY (UK) and $100,000/QALY (US) thresholds. OC incidence, BC incidence, and prevented deaths were estimated. RESULTS: Compared with clinical criteria/FH-based BRCA testing, BRCA1/BRCA2/RAD51C/RAD51D/BRIP1 germline testing and BRCA1/BRCA2 somatic testing of all patients with OC incorporating PARPi therapy had a UK ICER of £51,175/QALY (payer perspective) and £50,202/QALY (societal perspective) and a US ICER of $175,232/QALY (payer perspective) and $174,667/QALY (societal perspective), above UK/NICE and US cost-effectiveness thresholds in the base case. However, strategy A becomes cost-effective if PARPi costs decrease by 45% to 46% or if overall survival with PARPi reaches a hazard ratio of 0.28. Unselected panel germline testing alone (without PARPi therapy) is cost-effective, with payer-perspective ICERs of £11,291/QALY or $68,808/QALY and societal-perspective ICERs of £6,923/QALY or $65,786/QALY. One year's testing could prevent 209 UK BC/OC cases and 192 deaths, and 560 US BC/OC cases and 460 deaths. CONCLUSIONS: Unselected panel germline and somatic BRCA testing can become cost-effective, with a 45% to 46% reduction in PARPi costs. Regarding germline testing, unselected panel germline testing is highly cost-effective and should replace BRCA testing alone.


Assuntos
Carcinoma Epitelial do Ovário , Análise Custo-Benefício , Testes Genéticos , Mutação em Linhagem Germinativa , Neoplasias Ovarianas , Humanos , Feminino , Testes Genéticos/economia , Testes Genéticos/métodos , Carcinoma Epitelial do Ovário/genética , Carcinoma Epitelial do Ovário/economia , Carcinoma Epitelial do Ovário/diagnóstico , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/economia , Predisposição Genética para Doença , Proteína BRCA2/genética , Proteína BRCA1/genética , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Anos de Vida Ajustados por Qualidade de Vida , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Inibidores de Poli(ADP-Ribose) Polimerases/economia , RNA Helicases/genética , Adulto , Reino Unido/epidemiologia , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Proteínas de Ligação a DNA
5.
Cardiovasc Intervent Radiol ; 47(7): 857-862, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38844686

RESUMO

WHAT THIS PAPER ADDS: There is no reference in the literature regarding the transfer of patients between hospitals for interventional radiology procedures. This paper outlines an approach to assist with the safe assessment, reassessment and repatriation of patients requiring urgent procedures in a different hospital.


Assuntos
Segurança do Paciente , Transferência de Pacientes , Radiografia Intervencionista , Radiologia Intervencionista , Encaminhamento e Consulta , Humanos , Radiologia Intervencionista/métodos , Radiografia Intervencionista/métodos
6.
Genet Med ; 26(9): 101172, 2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38847192

RESUMO

PURPOSE: The identification of germline BRCA1/BRCA2 pathogenic variants (PV) infer high remaining lifetime breast/ovarian cancer risks, but there is paucity of studies assessing breast cancer risk after ovarian cancer diagnosis. METHODS: We reviewed the history of breast cancer in 895 PV heterozygotes (BRCA1 = 541). Cumulative annual breast cancer incidence was assessed at 2, 5, 10, and >10 years after ovarian cancer diagnosis date. RESULTS: Breast cancer annual rates were evaluated in 701 assessable women with no breast cancer at ovarian diagnosis (BRCA1 = 425). Incidence was lower at 2 years (1.18%) and 2 to 5 years (1.13%) but rose thereafter for BRCA1 with incidence post 10 years in excess of 4% annually. Breast cancer pathology in BRCA1 PV heterozygotes showed less high-grade triple-negative breast cancer and more lower-grade hormone-receptor-positive cancer than women with no prior ovarian cancer. In the prospective cohort from ovarian cancer diagnosis, <4% of all deaths were caused by breast cancer, although 50% of deaths in women with breast cancer after ovarian cancer diagnosis were due to breast cancer. CONCLUSION: Women can be reassured that incidence of breast cancer after ovarian cancer diagnosis is relatively low. It appears likely that this effect is due to platinum-based chemotherapy. Nonetheless women need to be aware that incidence increases thereafter, especially after 10 years.

7.
Int J Gynecol Cancer ; 34(7): 1034-1040, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38724236

RESUMO

OBJECTIVE: Cytotoxic chemotherapy for ovarian cancer can be augmented by co-administration of vascular endothelial growth factor inhibitors but these are contraindicated in patients with bowel obstruction due to the risk of gastrointestinal perforation. We evaluated the safety and feasibility of paclitaxel plus cediranib to treat patients with platinum-resistant ovarian cancer at risk of malignant bowel obstruction. METHODS: A phase II trial included eligible patients between March 2018 and February 2021, identified by clinical symptoms and radiographic risk factors for malignant bowel obstruction. Cediranib (20 mg/day) was added to paclitaxel (70 mg/m2/week) within 9 weeks of starting paclitaxel if pretreatment bowel symptoms had improved. The primary endpoint was the number of patients treated for ≥5 days with cediranib that were free of grade 3-5 gastrointestinal perforation or fistula. Secondary endpoints were hospitalization for bowel obstruction, grade ≥3 adverse events, treatment compliance assessed by relative dose intensity, objective response, progression-free survival, and overall survival. RESULTS: Thirty patients were recruited. Of these, 12 received paclitaxel alone and 17 received paclitaxel and cediranib in combination. One patient died before starting treatment. No patient developed a grade 3-5 gastrointestinal perforation or fistula (one sided 95% confidence interval (CI) upper limit 0.16). One patient required hospitalization for bowel obstruction but recovered with conservative management. The most common cediranib-related grade ≥3 adverse events were fatigue (3/17), diarrhorea (2/17), and hypomagnesemia (2/17). Relative dose intensity for paclitaxel was 90% (interquartile range (IQR) 85-100%; n=29) and for cediranib 88% (IQR 76-93%; n=17). The objective response in patients who received paclitaxel and cediranib was 65.0% (one complete and 10 partial responses). Median progression-free survival was 6.9 months (95% CI 4.4-11.5 months; n=17) and overall survival was 19.4 months (95% CI 10.1-20.4 months; n=17). Median follow-up was 12.4 months (8.9-not reached; n=17). CONCLUSIONS: The unexpectedly high withdrawal rate during paclitaxel alone, before introducing cediranib, meant we were unable to definitely conclude that paclitaxel plus cediranib did not cause gastrointestinal perforation or fistula. The regimen was however tolerated. TRIAL REGISTRATION NUMBER: EudraCT 2016-004618-93.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Obstrução Intestinal , Neoplasias Ovarianas , Paclitaxel , Quinazolinas , Humanos , Feminino , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/complicações , Idoso , Obstrução Intestinal/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quinazolinas/administração & dosagem , Quinazolinas/efeitos adversos , Resistencia a Medicamentos Antineoplásicos , Adulto , Esquema de Medicação , Carcinoma Epitelial do Ovário/tratamento farmacológico , Indóis
8.
Artigo em Inglês | MEDLINE | ID: mdl-38634675

RESUMO

Spontaneous intracranial hypotension is a rare but serious condition characterized by orthostatic headaches and a variety of neurological symptoms. 1,2 Spontaneous intracranial hypotension should be considered in all patients with new onset, daily, persistent headaches, and orthostatic symptoms. It is typically caused by spontaneous spinal cerebrospinal fluid (CSF) leaks. 1,2 Traditional first-line treatments include hydration, bedrest, epidural blood patches, and fibrin glue injections. However, refractory cases often require surgical intervention, especially those caused by a small ventral osteophyte, which is classified as a type 1 leak. 3-5 The small osteophyte causes a tear in the dura of the ventral canal, usually near the cervicothoracic junction. Diagnosis of these leaks is challenging because these small osteophytes can also occur asymptomatically, or patients may have several of them at multiple levels. Typically, dynamic myelography is needed for accurate localization due to the inadequacy of standard imaging. 6 This video details a young patient with refractory spontaneous intracranial hypotension from a type 1 spontaneous CSF leak, treated successfully using a posterior transdural surgical approach with spinal cord mobilization. Our video presentation outlines the surgical technique and provides an overview of this underdiagnosed condition. Our described approach offers direct visualization, suturing of the leak site, and a multilayer repair without the need for spinal fusion. It also avoids the morbidity to the neck, chest, and mediastinal structures that is at risk with lateral or anterior approaches. A combined intradural and extradural repair may enhance the durability of repair for ventral CSF leaks. The patient consented to the procedure. This operative video did not require Institutional Review Board approval as all patient information has been anonymized, ensuring no identifiable information is disclosed. The video is a single case that does not involve interventions or pose risks beyond standard care, adhering to ethical guidelines and institutional policies.

9.
Artigo em Inglês | MEDLINE | ID: mdl-38662179

RESUMO

People with mental illness are over-represented in the U.S. criminal legal system. Jail presents an optimal opportunity to provide needed mental health care as the entry point to corrections. However, there is a lack of programming available in jails, which may be partly due to limited understanding of how to successfully implement interventions in this complex setting. We implemented a nine-session psychotherapeutic intervention for people with serious mental illness in a county jail. As part of a larger implementation-effectiveness hybrid study, we gathered mixed-methods data from stakeholders (treatment recipients and jail administrators) on the feasibility and acceptability of the intervention's implementation. In focus group discussions and qualitative interviews, treatment recipients (n = 29) provided qualitative and quantitative data on their perceptions of the implementation's feasibility and acceptability. Jail administrators (n = 6) completed two quantitative self-report measures on their perceptions of the treatment's feasibility and acceptability. Qualitative analyses were conducted by two coders using inductive thematic template analysis; seven global themes relating to treatment recipients' perceptions of the assets and hindrances to feasibility and acceptability were developed and are presented with supporting quotations. Quantitatively, all treatment recipients endorsed the intervention's feasibility (100%), and nearly all (97%) endorsed its acceptability. On both self-report measures, jail administrators' mean scores fell above a-priori thresholds indicating feasibility and acceptability. We found qualitative and quantitative support for the use of this intervention in jail from both sets of stakeholders. These results have implications for clinical service and policy in jail, where service providers struggle to meet the considerable demand for mental health services.

10.
Aging Med (Milton) ; 7(1): 52-59, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38571673

RESUMO

Introduction: Addressing femoral neck fractures resulting from ground-level falls in older adults with Alzheimer's disease (AD) involves a personalized treatment plan. There is considerable ongoing debate concerning the relative advantages and disadvantages of surgical treatment (internal fixation or arthroplasty) vs nonoperative treatment for femoral neck fractures in older persons with AD. Methods: This retrospective cohort study compared the mortality, hazard ratio, and survival rate between operative and nonoperative treatments, controlling for patients' demographic information and baseline health status. The study population consisted of Optum beneficiaries diagnosed with AD who experienced an initial femoral neck fracture claim between January 1, 2012, and December 31, 2017. Kaplan-Meier survival curves were applied to compare the treatment groups' post-fracture survival rates and mortality. Cox regression was used to examine the survival period by controlling the covariates. Results: Out of the 4157 patients with AD with femoral neck fractures, 59.8% were women (n = 2487). The median age was 81 years. The 1-year survival rate for nonoperative treatment (70.19%) was lower than that for internal fixation (75.27%) and arthroplasty treatment (82.32%). Compared with the nonoperative group, arthroplasty surgical treatment had significant lower hazard risk of death (arthroplasty hazard ratio: 0.850, 95% CI: 0.728-0.991, P < 0.05). Discussion: The findings suggest that the operative treatment group experiences higher survival rates and lower mortality rates than the nonoperative group. This paper provides insights into treatment outcomes of older adults with AD receiving medical care for femoral neck fractures.

11.
bioRxiv ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38659923

RESUMO

The mechanisms of X chromosome inactivation suggest fundamental epigenetic differences between the female and male X chromosomes. However, DNA methylation studies often exclude the X chromosomes. In addition, many previous studies relied on techniques that examine non-randomly selected subsets of positions such as array-based methods, rather than assessing the whole X chromosome. Consequently, our understanding of X chromosome DNA methylation lags behind that of autosomes. Here we addressed this gap of knowledge by studying X chromosome DNA methylation using 89 whole genome bisulfite sequencing (WGBS) maps from neurons and oligodendrocytes. Using this unbiased and comprehensive data, we show that DNA methylation of the female X chromosomes is globally reduced (hypomethylated) across the entire chromosome compared to the male X chromosomes and autosomes. On the other hand, the majority of X-linked promoters were more highly methylated (hypermethylated) in females compared to males, consistent with the role of DNA methylation in X chromosome inactivation and dosage compensation. Remarkably, hypermethylation of female X promoters was limited to a group of previously lowly methylated promoters. The other group of highly methylated promoters were both hyper- and hypo-methylated in females with no obvious association with gene expression. Therefore, X chromosome inactivation by DNA methylation was exclusive to a subset of promoters with distinctive epigenetic feature. Apart from this group of promoters, differentially methylated regions in the female and male X chromosomes were dominated by female hypomethylation. Our study furthers the understanding of X-chromosome dosage regulation by DNA methylation on the chromosomal level as well as on individual gene level.

12.
BMJ Open ; 14(2): e084011, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38413157

RESUMO

INTRODUCTION: Falls in nursing homes are a major cause for decreases in residents' quality of life and overall health. This study aims to reduce resident falls by implementing the LOCK Falls Programme, an evidence-based quality improvement intervention. The LOCK Falls Programme involves the entire front-line care team in (1) focusing on evidence of positive change, (2) collecting data through systematic observation and (3) facilitating communication and coordination of care through the practice of front-line staff huddles. METHODS AND ANALYSIS: The study protocol describes a mixed-methods, 4-year hybrid (type 2) effectiveness-implementation study in State Veterans Homes in the USA. The study uses a pragmatic stepped-wedge randomised trial design and employs relational coordination theory and the Reach, Effectiveness, Adoption, Implementation and Maintenance framework to guide implementation and evaluation. A total of eight State Veterans Homes will participate and data will be collected over an 18-month period. Administrative data inclusive of all clinical assessments and Minimum Data Set assessments for Veterans with a State Veterans Home admission or stay during the study period will be collected (8480 residents total). The primary outcome is a resident having any fall. The primary analysis will be a partial intention-to-treat analysis using the rate of participants experiencing any fall. A staff survey (n=1200) and qualitative interviews with residents (n=80) and staff (n=400) will also be conducted. This research seeks to systematically address known barriers to nursing home quality improvement efforts associated with reducing falls. ETHICS AND DISSEMINATION: This study is approved by the Central Institutional Review Board (#167059-11). All participants will be recruited voluntarily and will sign informed consent as required. Collection, assessment and managing of solicited and spontaneously reported adverse events, including required protocol alterations, will be communicated and approved directly with the Central Institutional Review Board, the data safety monitoring board and the Office of Research and Development. Study results will be disseminated through peer-reviewed publications and conference presentations at the Academy Health Annual Research Meeting, the Gerontological Society of America Annual Scientific Meeting and the American Geriatrics Society Annual Meeting. Key stakeholders will also help disseminate lessons learnt. TRIAL REGISTRATION NUMBER: NCT05906095.


Assuntos
Qualidade de Vida , Veteranos , Humanos , Casas de Saúde , Melhoria de Qualidade
13.
JAMA Netw Open ; 7(2): e2356196, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38363569

RESUMO

Importance: The Hospital-Acquired Condition Reduction Program (HACRP) evaluates acute care hospitals on the occurrence of patient safety events and health care-associated infections. Since its implementation, several studies have raised concerns about the overpenalization of teaching and safety-net hospitals, and although several changes in the program's methodology have been applied in the last few years, whether these changes reversed the overpenalization of teaching and safety-net hospitals is unknown. Objective: To determine hospital characteristics associated with HACRP penalization and penalization reversal. Design, Setting, and Participants: This retrospective cross-sectional study assessed data from 3117 acute care hospitals participating in the HACRP. The HACRP penalization and hospital characteristics were obtained from Hospital Compare (2020 and 2021), the Inpatient Prospective Payment System impact file (2020), and the American Hospital Association annual survey (2018). Exposures: Hospital characteristics, including safety-net status and teaching intensity (no teaching and very minor, minor, major, and very major teaching levels). Main Outcomes and Measures: The primary outcome was HACRP penalization (ie, hospitals that fell within the worst quartile of the program's performance). Multivariable models initially included all covariates, and then backward stepwise variable selection was used. Results: Of 3117 hospitals that participated in HACRP in 2020, 779 (25.0%) were safety-net hospitals and 1090 (35.0%) were teaching institutions. In total, 771 hospitals (24.7%) were penalized. The HACRP penalization was associated with safety-net status (odds ratio [OR], 1.41 [95% CI, 1.16-1.71]) and very major teaching intensity (OR, 1.94 [95% CI, 1.15-3.28]). In addition, non-federal government hospitals were more likely to be penalized than for-profit hospitals (OR, 1.62 [95% CI, 1.23-2.14]), as were level I trauma centers (OR, 2.05 [95% CI, 1.43-2.96]) and hospitals located in the New England region (OR, 1.65 [95% CI, 1.12-2.43]). Safety-net hospitals with major teaching levels were twice as likely to be penalized as non-safety-net nonteaching hospitals (OR, 2.15 [95% CI, 1.14-4.03]). Furthermore, safety-net hospitals penalized in 2020 were less likely (OR, 0.64 [95% CI, 0.43-0.96]) to revert their HACRP penalization status in 2021. Conclusions and Relevance: Findings from this cross-sectional study indicated that teaching and safety-net hospital status continued to be associated with overpenalization in the HACRP despite recent changes in its methodology. Most of these hospitals were also less likely to revert their penalization status. A reevaluation of the program methodology is needed to avoid depleting resources of hospitals caring for underserved populations.


Assuntos
Doença Iatrogênica , Provedores de Redes de Segurança , Estados Unidos , Humanos , Estudos Retrospectivos , Estudos Transversais , Hospitais
15.
Gynecol Oncol ; 182: 124-131, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38262235

RESUMO

OBJECTIVE: Platinum-resistant epithelial ovarian cancer (EOC), recurrent endometrial cancer (EC), and triple negative breast cancer (TNBC) are difficult to treat after failing standard therapies. This phase I study evaluated mirvetuximab soravtansine (MIRV) and gemcitabine in patients with recurrent FRα-positive EOC, EC, or TNBC to determine the maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) (primary endpoint). METHODS: FRα-positive patients with platinum-resistant EOC, EC, or TNBC with ≤4 prior chemotherapy regimens (2 for EC) were enrolled. FRα expression requirement varied among eligible tumors and changed during the study. RESULTS: Twenty patients were enrolled; 17 were evaluable for DLT. Half the patients received ≥3 prior chemotherapy lines. Most EOC and EC patients (78%) were medium (50-74%) or high(75-100%) FRα expressors. TNBC patients were low (25-49%) FRα expressors. The MTD/RP2D was MIRV 6 mg/kg AIBW D1 and gemcitabine 800 mg/m2 IV, D1 and D8, every 21 days (Dose Level [DL] 3), where 5/7 patients demonstrated a partial response (PR) as their best response, including 2 confirmed ovarian responses whose time-to-progression and duration of response were 7.9/5.4 and 8.0/5.7 months respectively. Most common treatment-related adverse events at MTD were anemia and neutropenia (3/7 each, 43%), diarrhea, hypophosphatemia, thrombocytopenia, and leukopenia (2/7 each, 29%). DLTs were thrombocytopenia (DL1), oral mucositis (DL4) and diarrhea (DL4). Nine of 20 patients (45%; 95% CI: 21.1-68.9%) achieved PR as their best response, with 3/20 patients or 15% (95%CI, 0-32.1%) confirmed PR. CONCLUSION: MIRV and gemcitabine demonstrate promising activity in platinum resistant EOC at RP2D, but frequent hematologic toxicities.


Assuntos
Anticorpos Monoclonais Humanizados , Neoplasias do Endométrio , Imunoconjugados , Maitansina , Neoplasias Ovarianas , Trombocitopenia , Neoplasias de Mama Triplo Negativas , Feminino , Humanos , Gencitabina , Neoplasias Ovarianas/patologia , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/etiologia , Tubas Uterinas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/etiologia , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/etiologia , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias do Endométrio/etiologia , Diarreia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Maitansina/análogos & derivados
16.
Cardiovasc Intervent Radiol ; 47(2): 161-176, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38216742

RESUMO

BACKGROUND: Endoleaks represent the most common complication after EVAR. Some types are associated with ongoing risk of aneurysm rupture and necessitate long-term surveillance and secondary interventions. PURPOSE: This document, as with all CIRSE Standards of Practice documents, will recommend a reasonable approach to best practices of managing endoleaks. This will include imaging diagnosis, surveillance, indications for intervention, endovascular treatments and their outcomes. Our purpose is to provide recommendations based on up-to-date evidence, updating the guidelines previously published on this topic in 2013. METHODS: The writing group was established by the CIRSE Standards of Practice Committee and consisted of clinicians with internationally recognised expertise in endoleak management. The writing group reviewed the existing literature performing a pragmatic evidence search using PubMed to select publications in English and relating to human subjects up to 2023. The final recommendations were formulated through consensus. RESULTS: Endoleaks may compromise durability of the aortic repair, and long-term imaging surveillance is necessary for early detection and correct classification to guide potential re-intervention. The majority of endoleaks that require treatment can be managed using endovascular techniques. This Standards of Practice document provides up-to-date recommendations for the safe management of endoleaks.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Humanos , Endoleak/diagnóstico por imagem , Endoleak/terapia , Endoleak/etiologia , Correção Endovascular de Aneurisma , Implante de Prótese Vascular/métodos , Resultado do Tratamento , Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/métodos , Fatores de Risco , Estudos Retrospectivos
20.
Med Care ; 62(3): 132-139, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38036460

RESUMO

BACKGROUND: Some policymakers are concerned that expanding telehealth coverage may increase Medicare expenditures. However, there is limited evidence on the association of telehealth use with utilization and spending among Medicare beneficiaries with major depression. OBJECTIVE: To examine the differences in spending and utilization among telemental health users and non-telemental health users with major depression. METHODS: We examined 2014-2019 traditional Medicare claims data for beneficiaries aged ≥50 years with major depression in Texas. Multivariable generalized linear models were used to assess the relationships between telemental health use and Medicare spending and utilization while adjusting for patient demographics and programmatic and clinical factors. RESULTS: In each of the years between 2014 and 2019, an average of 4.6% Medicare beneficiaries with major depression had at least 1 telemental health visit. Compared with beneficiaries without a telemental health visit, those who had a telemental health visit were significantly more likely to be enrolled in Medicaid, be Medicare eligible due to a disability, live in a lower income area or in a rural area, and have a higher comorbidity index. Beneficiaries utilizing telemental health services incurred higher unadjusted Medicare spending than those not receiving telemental health services. However, this difference appeared due to beneficiary and programmatic characteristics rather than telemental health use. Adjusting for model covariates, the telemental health group had lower overall per member per year predicted spending, inpatient admissions, and emergency department visits than non-telemental health users. CONCLUSION: Our findings suggest that telemental health care use may improve access to mental health care without increasing Medicare spending among telemental health users in Texas.


Assuntos
Transtorno Depressivo Maior , Telemedicina , Idoso , Humanos , Estados Unidos , Medicare , Gastos em Saúde , Depressão
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